Aromatic prodrugs of propofol, compositions and uses thereof

ABSTRACT

Prodrugs of propofol, methods of making prodrugs of propofol, pharmaceutical compositions of prodrugs of propofol and methods of using prodrugs of propofol and pharmaceutical compositions thereof to treat or prevent diseases or disorders such as migraine headache pain and post-chemotherapy or post-operative surgery nausea and vomiting are disclosed herein.

1. FIELD

Disclosed herein are prodrugs of propofol, methods of making prodrugs ofpropofol, pharmaceutical compositions of prodrugs of propofol andmethods of using prodrugs of propofol and pharmaceutical compositionsthereof to treat or prevent diseases or disorders such as migraineheadache pain and post-chemotherapy or post-operative surgery nausea andvomiting.

2. BACKGROUND

Propofol (2,6-diisopropylphenol), (1), is a low molecular weight phenolthat is widely used as an intravenous sedative-hypnotic agent in theinduction and maintenance of anesthesia and/or sedation in mammals. Theadvantages of propofol as an anesthetic include rapid onset ofanesthesia, rapid clearance, and minimal side effects (Langley et al.,Drugs 1988, 35, 334-372). Propofol may mediate hypnotic effects throughinteraction with the GABA_(A) receptor complex, a heterooligomericligand-gated chloride ion channel (Peduto et al., Anesthesiology 1991,75, 1000-1009.).

Propofol is rapidly metabolized in mammals with the drug beingeliminated predominantly as glucuronidated and sulfated conjugates ofpropofol and 4-hydroxypropofol (Langley et al., Drugs 1988, 35,334-372). Propofol clearance exceeds liver blood flow, which indicatesthat extrahepatic tissues contribute to the overall metabolism of thedrug. Human intestinal mucosa glucuronidates propofol in vitro and oraldosing studies in rats indicate that approximately 90% of theadministered drug undergoes first pass metabolism, with extraction bythe intestinal mucosa accounting for the bulk of this presystemicelimination (Raoof et al., Pharm. Res. 1996, 13, 891-895). Accordingly,oral administration of propofol is of little therapeutic utility becauseof extensive first-pass metabolism.

Propofol has a broad range of biological and medical applications, whichare evident at sub-anesthetic doses and include treatment and/orprevention of intractable migraine headache pain (Krusz et al., Headache2000, 40, 224-230; Krusz, International Publication No. WO 00/54588).Propofol, when used to maintain anesthesia, causes a lower incidence ofpost-operative nausea and vomiting (“PONV”) in comparison to commoninhalational anesthetic agents; numerous controlled clinical studiessupport the anti-emetic activity of propofol (Tramer et al., Br. J.Anaesth. 1997, 78, 247-255; Brooker et al., Anaesth. Intensive Care1998, 26, 625-629; Gan et al., Anesthesiology 1997, 87, 779-784).Propofol also has anti-emetic activity when used in conjunction withchemotherapeutic compounds (Phelps et al., Ann. Pharmacother. 1996, 30,290-292; Borgeat et al., Oncology 1993, 50, 456-459; Borgeat et al.,Can. J. Anaesth. 1994, 41, 1117-1119; Tomioka et al., Anesth. Analg.1999, 89, 798-799). Nausea, retching and/or vomiting induced by avariety of chemotherapeutic agents (e.g., cisplatin, cyclophosphamide,5-fluorouracil, methotrexate, anthracycline drugs, etc.) has beencontrolled by low-dose propofol infusion in patients refractory toprophylaxis with conventional anti-emetic drugs (e.g., serotoninantagonists and corticosteroids).

Propofol may also be used to treat patients with refractory statusepilepticus (Brown et al., Pharmacother. 1998, 32, 1053-1059; Kuisma etal., Epilepsia 1995, 36, 1241-1243; Walder et al., Neurology 2002, 58,1327-1332; Sutherland et al., Anaesth. Intensive Care 1994, 22,733-737). Further, the anticonvulsant effects of propofol have also beendemonstrated in rat efficacy models at sub-anesthetic doses (Holtkamp etal., Ann. Neurol. 2001, 49, 260-263; Hasan et al., Pharmacol. Toxicol.1994, 74, 50-53).

Propofol may also be used as an antioxidant (Murphy et al., Br. J.Anaesth. 1992, 68, 613-618; Sagara et al., J. Neurochem. 1999, 73,2524-2530; Young et al., Eur. J. Anaesthesiol. 1997, 14, 320-326; Wanget al. Eur. J. Pharmacol. 2002, 452, 303-308). Propofol, at dosestypically used for surgical anesthesia, has observable antioxidanteffects in humans (De la Cruz et al., Anesth. Analg. 1999, 89,1050-1055). Pathogenesis or subsequent damage pathways in variousneurodegenerative diseases involve reactive oxygen species andaccordingly may be treated or prevented with antioxidants (Simonian etal., Pharmacol. Toxicol. 1996, 36, 83-106). Examples of specificneurodegenerative diseases which may be treated or prevented withanti-oxidants include, but are not limited to, Friedrich's disease,Parkinson's disease, Alzheimer's disease, Huntington's disease,amyotrophic lateral sclerosis (“ALS”), multiple sclerosis (“MS”), Pickdisease, inflammatory diseases and diseases caused by inflammatorymediators such as tumor necrosis factor (TNF) and IL-1.

A significant problem with the therapeutic use of propofol is its lackof appreciable solubility in water. Accordingly, propofol must bespecially formulated in aqueous media using solubilizers or emulsifiers(Briggs et al., Anaesthesia 1982, 37, 1099-1101). For example, in acurrent commercial product (Diprivan®, Astra-Zeneca) an oil-in-wateremulsion (the emulsifier is the lecithin mixture Intralipid®), is usedto formulate propofol (Picard et al., Anesth. Analg. 2000, 90, 963-969).

One potential solution to the insolubility of propofol in aqueoussolution, which avoids the use of additives, solubilizers oremulsifiers, is a water-soluble, stable propofol prodrug that isconverted to propofol in vivo. (Hendler et al., InternationalPublication No. WO 99/58555; Morimoto et al., International PublicationNo. WO 00/48572; Hendler et al., U.S. Pat. No. 6,254,853; Stella et al.,U.S. Patent Application No. US2001/0025035; Hendler, United StatesPatent Application No. 6,362,234; International Publication No. WO02/13810; Sagara et al., J. Neurochem. 1999, 73, 2524-2530; Banaszczyket al., Anesth. Analg. 2002, 95, 1285-1292; Trapani et al., Int. J.Pharm. 1998, 175, 195-204; Trapani et al., J. Med. Chem. 1998, 41,1846-1854; Anderson et al., J. Med. Chem. 2001, 44, 3582-3591; Pop etal., Med. Chem. Res. 1992, 2, 16-21). A significant problem withexisting propofol prodrugs is their stability under physiologicalconditions, which prevents release of therapeutically significantconcentrations of propofol, particularly when the prodrug is orallyadministered. Thus, there is a need for propofol prodrugs, which aresufficiently labile under physiological conditions to providetherapeutically significant concentrations of propofol, particularly,when the prodrug is orally administered.

3. SUMMARY

These and other needs are met by providing prodrugs of propofol, methodsof making prodrugs of propofol, pharmaceutical compositions of prodrugsof propofol and methods of using prodrugs of propofol and pharmaceuticalcompositions thereof to treat or prevent diseases or disorders such asmigraine headache pain, neurodegenerative disorders andpost-chemotherapy or post-operative surgery nausea and vomiting. In someembodiments, prodrugs of propofol and pharmaceutical compositionsthereof are orally administered. In other embodiments, prodrugs ofpropofol are translocated across the gastrointestinal mucosa viainteraction with transporter proteins expressed within enterocyteslining the gastrointestinal tract.

In a first aspect, a compound of structural Formula (I) is provided:

-   -   or pharmaceutically acceptable salts, hydrates, solvates or        N-oxides thereof, wherein:    -   n is 0 or 1;    -   Y is selected from the group consisting of a bond, CR¹R², NR³, O        and S;    -   A is CR⁴ or N;    -   B is CR⁵ or N;    -   D is CR⁶ or N;    -   E is CR⁷ or N;    -   G is CR⁸ or N;    -   R¹⁸ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxycarbonyl, aryl, substituted aryl,        arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, heteroaryl,        substituted heteroaryl and heteroarylalkyl;    -   R¹ and R² are independently selected from the group consisting        of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl,        arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl,        heteroaryl, substituted heteroaryl and heteroarylalkyl;    -   R³ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;    -   R⁴ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁵ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁶ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁷ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁸ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   W is selected from the group consisting of a bond, CR¹²R¹³,        NR¹⁴, O and S;    -   Z is selected from the group consisting of CR¹⁵R¹⁶, NR¹⁷, O and        S;    -   k is 0 or 1;    -   r is 1, 2 or 3;    -   each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁵ and R¹⁶ is independently        selected from the group consisting of hydrogen, alkyl,        substituted alkyl, aryl, substituted aryl, arylalkyl,        cycloalkyl, substituted cycloalkyl, cycloheteroalkyl,        heteroaryl, substituted heteroaryl and heteroarylalkyl;    -   R¹⁴ and R¹⁷ are independently selected from the group consisting        of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl,        cycloalkyl and heteroaryl;    -   with the provisos that:    -   at least one of A, B, D, E and G is not N;    -   one and only one of R⁴, R⁵, R⁶, R⁷ or R⁸ is        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   and if k is 0 then W is a bond.

In a second aspect pharmaceutical compositions are provided, whichgenerally comprise one or more compounds disclosed herein, and apharmaceutically acceptable vehicle such as a diluent, carrier,excipient or adjuvant. The choice of diluent, carrier, excipient andadjuvant will depend upon, among other factors, the desired mode ofadministration. In some embodiments, the mode of administration is oral.

In a third aspect, methods for treating or preventing various diseasesor disorders including, but not limited to migraine headache pain,post-chemotherapy or post-operative surgery nausea and vomiting andneurodegenerative disorders (e.g., epilepsy, Friedrich's disease,Parkinson's disease, Alzheimer's disease, Huntington's disease,amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS) and Pickdisease) are provided. The methods generally involve administering to apatient in need of such treatment or prevention a therapeuticallyeffective amount of a compound disclosed herein and/or pharmaceuticalcompositions thereof.

In a fourth aspect, methods for inducing and/or maintaining anesthesiaor sedation in a mammal are provided. The methods generally involveadministering to a patient in need of such anesthesia sedation inductionand/or maintenance a therapeutically effective amount of a compounddisclosed herein and/or pharmaceutical compositions thereof.

4. DETAILED DESCRIPTION 4.1 Definitions

“Alkyl” by itself or as part of another substituent refers to asaturated or unsaturated, branched, straight-chain or cyclic monovalenthydrocarbon radical derived by the removal of one hydrogen atom from asingle carbon atom of a parent alkane, alkene or alkyne. Typical alkylgroups include, but are not limited to, methyl; ethyls such as ethanyl,ethenyl, ethynyl; propyls such as propan-1-yl, propan-2-yl,cyclopropan-1-yl, prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl(allyl), cycloprop-1-en-1-yl; cycloprop-2-en-1-yl, prop-1-yn-1-yl,prop-2-yn-1-yl, etc.; butyls such as butan-1-yl, butan-2-yl,2-methyl-propan-1-yl, 2-methyl-propan-2-yl, cyclobutan-1-yl,but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl, but-2-en-1-yl,but-2-en-2-yl, buta-1,3-dien-1-yl, buta-1,3-dien-2-yl,cyclobut-1-en-1-yl, cyclobut-1-en-3-yl, cyclobuta-1,3-dien-1-yl,but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

The term “alkyl” is specifically intended to include groups having anydegree or level of saturation, i.e., groups having exclusively singlecarbon-carbon bonds, groups having one or more double carbon-carbonbonds, groups having one or more triple carbon-carbon bonds and groupshaving mixtures of single, double and triple carbon-carbon bonds. Wherea specific level of saturation is intended, the expressions “alkanyl,”“alkenyl,” and “alkynyl” are used. In some embodiments, an alkyl groupcomprises from 1 to 20 carbon atoms. In other embodiments, an alkylgroup comprises from 1 to 10 carbon atoms. In still other embodiments,an alkyl group comprises from 1 to 10 carbon atoms.

“Alkanyl” by itself or as part of another substituent refers to asaturated branched, straight-chain or cyclic alkyl radical derived bythe removal of one hydrogen atom from a single carbon atom of a parentalkane. Typical alkanyl groups include, but are not limited to,methanyl; ethanyl; propanyls such as propan-1-yl, propan-2-yl(isopropyl), cyclopropan-1-yl, etc.; butanyls such as butan-1-yl,butan-2-yl (sec-butyl), 2-methyl-propan-1-yl (isobutyl),2-methyl-propan-2-yl (t-butyl), cyclobutan-1-yl, etc.; and the like.

“Alkenyl” by itself or as part of another substituent refers to anunsaturated branched, straight-chain or cyclic alkyl radical having atleast one carbon-carbon double bond derived by the removal of onehydrogen atom from a single carbon atom of a parent alkene. The groupmay be in either the cis or trans conformation about the double bond(s).Typical alkenyl groups include, but are not limited to, ethenyl;propenyls such as prop-1-en-1-yl, prop-1-en-2-yl, prop-2-en-1-yl(allyl), prop-2-en-2-yl, cycloprop-1-en-1-yl; cycloprop-2-en-1-yl;butenyls such as but-1-en-1-yl, but-1-en-2-yl, 2-methyl-prop-1-en-1-yl,but-2-en-1-yl, but-2-en-1-yl, but-2-en-2-yl, buta-1,3-dien-1-yl,buta-1,3-dien-2-yl, cyclobut-1-en-1-yl, cyclobut-1-en-3-yl,cyclobuta-1,3-dien-1-yl, etc.; and the like.

“Alkynyl” by itself or as part of another substituent refers to anunsaturated branched, straight-chain or cyclic alkyl radical having atleast one carbon-carbon triple bond derived by the removal of onehydrogen atom from a single carbon atom of a parent alkyne. Typicalalkynyl groups include, but are not limited to, ethynyl; propynyls suchas prop-1-yn-1-yl, prop-2-yn-1-yl, etc.; butynyls such as but-1-yn-1-yl,but-1-yn-3-yl, but-3-yn-1-yl, etc.; and the like.

“Acyl” by itself or as part of another substituent refers to a radical—C(O)R³⁰, where R³⁰ is hydrogen, alkyl, cycloalkyl, cycloheteroalkyl,aryl, arylalkyl, heteroalkyl, heteroaryl, heteroarylalkyl as definedherein. Representative examples include, but are not limited to formyl,acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl,benzylcarbonyl and the like.

“Alkoxy” by itself or as part of another substituent refers to a radical—OR³¹ where R³¹ represents an alkyl or cycloalkyl group as definedherein. Representative examples include, but are not limited to,methoxy, ethoxy, propoxy, butoxy, cyclohexyloxy and the like.

“Alkoxycarbonyl” by itself or as part of another substituent, refers toa radical —C(O)OR³¹ where R³¹ is as defined above.

“Aryl” by itself or as part of another substituent refers to amonovalent aromatic hydrocarbon radical derived by the removal of onehydrogen atom from a single carbon atom of a parent aromatic ringsystem. Typical aryl groups include, but are not limited to, groupsderived from aceanthrylene, acenaphthylene, acephenanthrylene,anthracene, azulene, benzene, chrysene, coronene, fluoranthene,fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene,indane, indene, naphthalene, octacene, octaphene, octalene, ovalene,penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene,phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene,triphenylene, trinaphthalene and the like. In some embodiment, an arylgroup comprises from 6 to 20 carbon atoms. In other embodiments, andaryl group comprises from 6 to 12 carbon atoms.

“Arylalkyl” by itself or as part of another substituent refers to anacyclic alkyl radical in which one of the hydrogen atoms bonded to acarbon atom, typically a terminal or sp³ carbon atom, is replaced withan aryl group. Typical arylalkyl groups include, but are not limited to,benzyl, 2-phenylethan-1-yl, 2-phenylethen-1-yl, naphthylmethyl,2-naphthylethan-1-yl, 2-naphthylethen-1-yl, naphthobenzyl,2-naphthophenylethan-1-yl and the like. Where specific alkyl moietiesare intended, the nomenclature arylalkanyl, arylalkenyl and/orarylalkynyl is used. In some embodiments, an arylalkyl group is (C₆-C₃₀)arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkylgroup is (C₁-C₁₀) and the aryl moiety is (C₆-C₂₀). In other embodiments,an arylalkyl group is (C₆-C₂₀) arylalkyl, e.g., the alkanyl, alkenyl oralkynyl moiety of the arylalkyl group is (C₁-C₈) and the aryl moiety is(C₆-C₁₂).

“Carbamoyl” by itself or as part of another substituent refers to theradical —C(O)N(R³²)R³³ where R³² and R³³ are independently hydrogen,alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substitutedarylalkyl, heteroarylalkyl, substituted heteroarylalkyl, heteroaryl orsubstituted heteroaryl, as defined herein.

“Compounds” refers to compounds encompassed by the generic formulaedisclosed herein and includes any specific compounds within thoseformulae whose structure is disclosed herein. Compounds may beidentified either by their chemical structure and/or chemical name. Whenthe chemical structure and chemical name conflict, the chemicalstructure is determinative of the identity of the compound. Compoundsdisclosed herein may contain one or more chiral centers and/or doublebonds and therefore, may exist as stereoisomers, such as double-bondisomers (i.e., geometric isomers), enantiomers or diastereomers.Accordingly, when stereochemistry at chiral centers is not specified,the chemical structures depicted herein encompass all possibleconfigurations at those chiral centers including the stereoisomericallypure form (e.g., geometrically pure, enantiomerically pure ordiastereomerically pure) and enantiomeric and stereoisomeric mixtures.Enantiomeric and stereoisomeric mixtures can be resolved into theircomponent enantiomers or stereoisomers using separation techniques orchiral synthesis techniques well known to the skilled artisan. Compoundsdisclosed herein may also exist in several tautomeric forms includingthe enol form, the keto form and mixtures thereof. Accordingly, thechemical structures depicted herein encompass all possible tautomericforms of the illustrated compounds. Compounds disclosed herein alsoinclude isotopically labeled compounds where one or more atoms have anatomic mass different from the atomic mass conventionally found innature. Examples of isotopes that may be incorporated into the compoundsdisclosed herein include, but are not limited to, ²H, ³H, ¹¹C, ¹³C, ¹⁴C,¹⁵N, ¹⁷O and ¹⁸O. Compounds disclosed herein may exist in unsolvatedforms as well as solvated forms, including hydrated forms and asN-oxides. In general, the hydrated, solvated and N-oxide forms arewithin the scope of the present disclosure. Certain compounds disclosedherein may exist in multiple crystalline or amorphous forms. In general,all physical forms are equivalent for the uses contemplated herein andare intended to be within the scope of the present disclosure. Further,it should be understood, when partial structures of compounds areillustrated, that brackets indicate the point of attachment of thepartial structure to the rest of the molecule.

“Cycloalkyl” by itself or as part of another substituent refers to asaturated or unsaturated cyclic alkyl radical. Where a specific level ofsaturation is intended, the nomenclature “cycloalkanyl” or“cycloalkenyl” is used. Typical cycloalkyl groups include, but are notlimited to, groups derived from cyclopropane, cyclobutane, cyclopentane,cyclohexane, and the like. Preferably, the cycloalkyl group is (C₃-C₁₀)cycloalkyl, more preferably (C₃-C₇) cycloalkyl.

“Cycloheteroalkyl” by itself or as part of another substituent refers toa saturated or unsaturated cyclic alkyl radical in which one or morecarbon atoms (and any associated hydrogen atoms) are independentlyreplaced with the same or different heteroatom. Typical heteroatoms toreplace the carbon atom(s) include, but are not limited to, N, P, O, S,Si, etc. Where a specific level of saturation is intended, thenomenclature “cycloheteroalkanyl” or “cycloheteroalkenyl” is used.Typical cycloheteroalkyl groups include, but are not limited to, groupsderived from epoxides, azirines, thiiranes, imidazolidine, morpholine,piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine, and thelike.

“Heteroalkyl, Heteroalkanyl, Heteroalkenyl and Heteroalkynyl” bythemselves or as part of another substituent refer to alkyl, alkanyl,alkenyl and alkynyl groups, respectively, in which one or more of thecarbon atoms (and any associated hydrogen atoms) are independentlyreplaced with the same or different heteroatomic groups. Typicalheteroatomic groups which can be included in these groups include, butare not limited to, —O—, —S—, —O—O—, —S—S—, —O—S—, —NR³⁴R³⁵—, ═N—N═,—N═N—, —N═N—NR³⁶R³⁷, —PR³⁸—, —P(O)₂—, —POR³⁹—, —O—P(O)₂—, —SO—, —SO₂—,—SnR⁴⁰R⁴¹— and the like, where R³⁴, R³⁵, R³⁶, R³⁷, R³⁸, R³⁹, R⁴⁰ and R⁴¹are independently hydrogen, alkyl, substituted alkyl, aryl, substitutedaryl, arylalkyl, substituted arylalkyl, cycloalkyl, substitutedcycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl,substituted heteroalkyl, heteroaryl, substituted heteroaryl,heteroarylalkyl or substituted heteroarylalkyl.

“Heteroaryl” by itself or as part of another substituent refers to amonovalent heteroaromatic radical derived by the removal of one hydrogenatom from a single atom of a parent heteroaromatic ring system. Typicalheteroaryl groups include, but are not limited to, groups derived fromacridine, arsindole, carbazole, β-carboline, chromane, chromene,cinnoline, furan, imidazole, indazole, indole, indoline, indolizine,isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline,isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine,phenanthridine, phenanthroline, phenazine, phthalazine, pteridine,purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine,pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline,tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, and thelike. In some embodiments, the heteroaryl group is from 5-20 memberedheteroaryl. In other embodiments, the heteroaryl group is from 5-10membered heteroaryl. Preferred heteroaryl groups are those derived fromthiophene, pyrrole, benzothiophene, benzofuran, indole, pyridine,quinoline, imidazole, oxazole and pyrazine.

“Heteroarylalkyl” by itself or as part of another substituent refers toan acyclic alkyl radical in which one of the hydrogen atoms bonded to acarbon atom, typically a terminal or sp³ carbon atom, is replaced with aheteroaryl group. Where specific alkyl moieties are intended, thenomenclature heteroarylalkanyl, heteroarylalkenyl and/orheteroarylalkynyl is used. In some embodiments, the heteroarylalkylgroup is a 6-30 membered heteroarylalkyl, e.g., the alkanyl, alkenyl oralkynyl moiety of the heteroarylalkyl is 1-10 membered and theheteroaryl moiety is a 5-20-membered heteroaryl. In other embodiments,the heteroarylalkyl group is 6-20 membered heteroarylalkyl, e.g., thealkanyl, alkenyl or alkynyl moiety of the heteroarylalkyl is 1-8membered and the heteroaryl moiety is a 5-12-membered heteroaryl.

“Parent Aromatic Ring System” refers to an unsaturated cyclic orpolycyclic ring system having a conjugated π electron system.Specifically included within the definition of “parent aromatic ringsystem” are fused ring systems in which one or more of the rings arearomatic and one or more of the rings are saturated or unsaturated, suchas, for example, fluorene, indane, indene, phenalene, etc. Typicalparent aromatic ring systems include, but are not limited to,aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene,benzene, chrysene, coronene, fluoranthene, fluorene, hexacene,hexaphene, hexalene, as-indacene, s-indacene, indane, indene,naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene,pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene,picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene,trinaphthalene and the like.

“Parent Heteroaromatic Ring System” refers to a parent aromatic ringsystem in which one or more carbon atoms (and any associated hydrogenatoms) are independently replaced with the same or different heteroatom.Typical heteroatoms to replace the carbon atoms include, but are notlimited to, N, P, O, S, Si, etc. Specifically included within thedefinition of “parent heteroaromatic ring systems” are fused ringsystems in which one or more of the rings are aromatic and one or moreof the rings are saturated or unsaturated, such as, for example,arsindole, benzodioxan, benzofuran, chromane, chromene, indole,indoline, xanthene, etc. Typical parent heteroaromatic ring systemsinclude, but are not limited to, arsindole, carbazole, β-carboline,chromane, chromene, cinnoline, furan, imidazole, indazole, indole,indoline, indolizine, isobenzofuran, isochromene, isoindole,isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine,oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline,phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole,pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline,quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole,thiophene, triazole, xanthene, and the like.

“Pharmaceutical composition” refers to at least one compound disclosedherein and a pharmaceutically acceptable vehicle, with which thecompound is administered to a patient.

“Pharmaceutically acceptable salt” refers to a salt of a compounddisclosed herein, which possesses the desired pharmacological activityof the parent compound. Such salts include: (1) acid addition salts,formed with inorganic acids such as hydrochloric acid, hydrobromic acid,sulfuric acid, nitric acid, phosphoric acid, and the like; or formedwith organic acids such as acetic acid, propionic acid, hexanoic acid,cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid,malonic acid, succinic acid, malic acid, maleic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl) benzoicacid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonicacid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid,benzenesulfonic acid, 4-chlorobenzenesulfonic acid,2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonicacid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonicacid, 3-phenylpropionic acid, trimethylacetic acid, tertiary butylaceticacid, lauryl sulfuric acid, gluconic acid, glutamic acid,hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, andthe like; or (2) salts formed when an acidic proton present in theparent compound is replaced by a metal ion, e.g., an alkali metal ion,an alkaline earth ion, or an aluminum ion; or coordinates with anorganic base such as ethanolamine, diethanolamine, triethanolamine,N-methylglucamine and the like.

“Pharmaceutically acceptable vehicle” refers to a diluent, adjuvant,excipient or carrier with which a compound is administered.

“Patient” includes humans. The terms “human” and “patient” are usedinterchangeably herein.

“Preventing” or “prevention” refers to a reduction in risk of acquiringa disease or disorder (i.e., causing at least one of the clinicalsymptoms of the disease not to develop in a patient that may be exposedto or predisposed to the disease but does not yet experience or displaysymptoms of the disease).

“Prodrug” refers to a derivative of a drug molecule that requires atransformation within the body to release the active drug. Prodrugs arefrequently, although not necessarily, pharmacologically inactive untilconverted to the parent drug. A hydroxyl containing drug may beconverted to, for example, to an ester, carbonate, acyloxyalkyl or asulfonate prodrug, which may be hydrolyzed in vivo to provide thehydroxyl compound. Prodrugs for drugs with functional groups differentthan those listed above are well known to the skilled artisan.

“Promoiety” refers to a form of protecting group that when used to maska functional group within a drug molecule converts the drug into aprodrug. Typically, the promoiety will be attached to the drug viabond(s) that are cleaved by enzymatic or non-enzymatic means in vivo.

“Protecting group” refers to a grouping of atoms that when attached to areactive functional group in a molecule masks, reduces or preventsreactivity of the functional group. Examples of protecting groups can befound in Green et al., “Protective Groups in Organic Chemistry”, (Wiley,2^(nd) ed. 1991) and Harrison et al., “Compendium of Synthetic OrganicMethods”, Vols. 1-8 (John Wiley and Sons, 1971-1996). Representativeamino protecting groups include, but are not limited to, formyl, acetyl,trifluoroacetyl, benzyl, benzyloxycarbonyl (“CBz”), tert-butoxycarbonyl(“Boc”), trimethylsilyl (“TMS”), 2-trimethylsilyl-ethanesulfonyl(“SES”), trityl and substituted trityl groups, allyloxycarbonyl,9-fluorenylmethyloxycarbonyl (“FMOC”), nitro-veratryloxycarbonyl(“NVOC”) and the like. Representative hydroxyl protecting groupsinclude, but are not limited to, those where the hydroxyl group iseither acylated or alkylated such as benzyl, and trityl ethers as wellas alkyl ethers, tetrahydropyranyl ethers, trialkylsilyl ethers andallyl ethers.

“SMVT” refers to the sodium-dependent multivitamin transporter (SLC5A6).Genes encoding this transporter have been cloned from rat, human andrabbit tissue (see Prasad et al., J. Biol. Chem. 1998, 273, 7501-7506;Wang et al., J. Biol. Chem. 1999, 274, 14875-14883; Chatterjee et al.,Am. J. Physiol. 1999, 277, C605-C613; Prasad et al., Arch. Biochem.Biophys. 1999, 366, 95-106).

“Substituted” refers to a group in which one or more hydrogen atoms areindependently replaced with the same or different substituent(s).Typical substituents include, but are not limited to, -M, —R⁶⁰, —O⁻, ═O,—OR⁶⁰, —SR⁶⁰, —S⁻, ═S, —NR⁶⁰R⁶¹, ═NR⁶⁰, —CF₃, —CN, —OCN, —SCN, —NO,—NO₂, ═N₂, —N₃, —S(O)₂O⁻, —S(O)₂OH, —S(O)₂R⁶⁰, —OS(O₂)O⁻, —OS(O)₂R⁶⁰,—P(O)(O⁻)₂, —P(O)(OR⁶⁰)(O⁻), —OP(O)(OR⁶⁰)(OR⁶¹), —C(O)R⁶⁰, —C(S)R⁶⁰,—C(O)OR⁶⁰, —C(O)NR⁶⁰R⁶¹, —C(O)O⁻, —C(S)OR⁶⁰, —NR⁶²C(O)NR⁶⁰R⁶¹,—NR⁶²C(S)NR⁶⁰R⁶¹, —NR⁶²C(NR⁶³)NR⁶⁰R⁶¹ and —C(NR⁶²)NR⁶⁰R⁶¹ where M isindependently a halogen; R⁶⁰, R⁶¹, R⁶² and R⁶³ are independentlyhydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy,cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substitutedcycloheteroalkyl, aryl, substituted aryl, heteroaryl or substitutedheteroaryl, or optionally R⁶⁰ and R⁶¹ together with the nitrogen atom towhich they are bonded form a cycloheteroalkyl or substitutedcycloheteroalkyl ring; and R⁶⁴ and R⁶⁵ are independently hydrogen,alkyl, substituted alkyl, aryl, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl,heteroaryl or substituted heteroaryl, or optionally R⁶⁴ and R⁶⁵ togetherwith the nitrogen atom to which they are bonded form a cycloheteroalkylor substituted cycloheteroalkyl ring. Preferably, substituents include-M, —R⁶⁰, ═O, —OR⁶⁰, —SR⁶⁰, —S⁻, ═S, —NR⁶⁰R⁶¹, ═NR⁶⁰, —CF₃, —CN, —OCN,—SCN, —NO, —NO₂, ═N₂, —N₃, —S(O)₂R⁶⁰, —OS(O₂)O⁻, —OS(O)₂R⁶⁰, —P(O)(O⁻)₂,—P(O)(OR⁶⁰)(O⁻), —OP(O)(OR⁶⁰)(OR⁶¹), —C(O)R⁶⁰, —C(S)R⁶⁰, —C(O)OR⁶⁰,—C(O)NR⁶⁰R⁶¹, —C(O)O⁻, —NR⁶²C(O)NR⁶⁰R⁶¹, more preferably, -M, —R⁶⁰, ═O,—OR⁶⁰, —SR⁶⁰, —NR⁶⁰R⁶¹, —CF₃, —CN, —NO₂, —S(O)₂R⁶⁰, —P(O)(OR⁶⁰)(OR⁻),—OP(O)(OR⁶⁰)(OR⁶¹), —C(O)R⁶⁰, —C(O)OR⁶⁰, —C(O)NR⁶⁰R⁶¹, —C(O)O⁻, mostpreferably, -M, —R⁶⁰, ═O, —OR⁶⁰, —SR⁶⁰, —NR⁶⁰R⁶¹, —CF₃, —CN, —NO₂,—S(O)₂R⁶⁰, —OP(O)(OR⁶⁰)(OR⁶¹), —C(O)R⁶⁰, —C(O)OR⁶⁰, —C(O)O⁻, where R⁶⁰,R⁶¹ and R⁶² are as defined above.

“Transported by the SMVT transporter” refers to the translocation of amolecule across a membrane of a cell expressing the SMVT transporter.The translocation occurs through interaction with the transporter and isenergized by cotransport of Na⁺ ions across the membrane.

“Treating” or “treatment” of any disease or disorder refers, In someembodiments, to ameliorating the disease or disorder (i.e., arresting orreducing the development of the disease or at least one of the clinicalsymptoms thereof). In other embodiments “treating” or “treatment” refersto ameliorating at least one physical parameter, which may not bediscernible by the patient. In yet another embodiment, “treating” or“treatment” refers to inhibiting the disease or disorder, eitherphysically, (e.g., stabilization of a discernible symptom),physiologically, (e.g., stabilization of a physical parameter), or both.In yet another embodiment, “treating” or “treatment” refers to delayingthe onset of the disease or disorder.

“Therapeutically effective amount” means the amount of a compound that,when administered to a patient for treating a disease, is sufficient toeffect such treatment for the disease. The “therapeutically effectiveamount” will vary depending on the compound, the disease and itsseverity and the age, weight, etc., of the patient to be treated.

Reference will now be made in detail to various embodiments of theinvention. While the invention will be described in conjunction withthese embodiments, it will be understood that it is not intended tolimit the invention to those embodiments. To the contrary, it isintended to cover alternatives, modifications, and equivalents as may beincluded within the spirit and scope of the invention as defined by theappended claims.

5.2 Compounds

The compounds disclosed herein are prodrugs of propofol. In someembodiments, the compounds are orally administered. In some embodiments,the compounds are able to pass across the gastrointestinal tract. Inother embodiments, prodrugs of propofol are translocated across thegastrointestinal mucosa via interaction with transporter proteinsexpressed within enterocytes lining the gastrointestinal tract.

In some embodiments, compounds of structural Formula (I) are provided:

-   -   or pharmaceutically acceptable salts, hydrates, solvates or        N-oxides thereof, wherein:    -   n is 0 or 1;    -   Y is selected from the group consisting of a bond, CR¹R², NR³, O        and S;    -   A is CR⁴ or N;    -   B is CR⁵ or N;    -   D is CR⁶ or N;    -   E is CR⁷ or N;    -   G is CR⁸ or N;    -   R¹⁸ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxycarbonyl, aryl, substituted aryl,        arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, heteroaryl,        substituted heteroaryl and heteroarylalkyl;    -   R¹ and R² are independently selected from the group consisting        of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl,        arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl,        heteroaryl, substituted heteroaryl and heteroarylalkyl;    -   R³ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl;    -   R⁴ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁵ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁶ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁷ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   R⁸ is selected from the group consisting of hydrogen, alkyl,        substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl,        aryl, substituted aryl, arylalkyl, carboxyl, cycloalkyl,        substituted cycloalkyl, cycloheteroalkyl, halo, heteroaryl,        substituted heteroaryl, heteroarylalkyl, hydroxyl and        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   W is selected from the group consisting of a bond, CR¹²R¹³,        NR¹⁴, O and S;    -   Z is selected from the group consisting of CR¹⁵R¹⁶, NR¹⁷, O and        S;    -   k is 0 or 1;    -   r is 1, 2 or 3;    -   each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁵ and R¹⁶ is independently        selected from the group consisting of hydrogen, alkyl,        substituted alkyl, aryl, substituted aryl, arylalkyl,        cycloalkyl, substituted cycloalkyl, cycloheteroalkyl,        heteroaryl, substituted heteroaryl and heteroarylalkyl;    -   R¹⁴ and R¹⁷ are independently selected from the group consisting        of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl,        cycloalkyl and heteroaryl;    -   with the provisos that:    -   at least one of A, B, D, E and G is not N;    -   one and only one of R⁴, R⁵, R⁶, R⁷ or R⁸ is        —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹;    -   and if k is 0 then W is a bond.

In some embodiments of a compound of Formula (I), n is 0. In otherembodiments of a compound of Formula (I), n is 1.

In still other embodiments of a compound of Formula (I), n is 1 and R¹⁸is selected from the group consisting of hydrogen, alkyl, substitutedalkyl, aryl, substituted aryl, arylalkyl, cycloalkyl and heteroaryl.

In the above embodiment, R¹⁸ is selected from the group consisting ofhydrogen, alkyl and substituted alkyl. Preferably, R¹⁸ is selected fromthe group consisting of hydrogen and C₁₋₄ alkyl. More preferably, R¹⁸ ishydrogen or methyl.

In the above embodiment, R¹⁸ is selected from the group consisting ofhydrogen, aryl and substituted aryl. Preferably, R¹⁸ is selected fromthe group consisting of hydrogen, phenyl and substituted phenyl.

In the above embodiment, R¹⁸ is selected from the group consisting ofhydrogen, arylalkyl and substituted arylalkyl. Preferably, R¹⁸ isselected from the group consisting of hydrogen, benzyl and substitutedbenzyl.

In still other embodiments of a compound of Formula (I), Y is a bond.

In still other embodiments of a compound of Formula (I), Y is CR¹R² andR¹ and R² are independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R¹ and R² are independently hydrogen or alkanyl.More preferably, R¹ and R² are independently hydrogen or methyl.

In still other embodiments of a compound of Formula (I), Y is NR³ and R³is hydrogen or alkanyl. More preferably, R³ is hydrogen or methyl.

In still other embodiments of a compound of Formula (I), Y is O.

In still other embodiments of a compound of Formula (I), Y is S.

In still other embodiments of a compound of Formula (I), A is CR⁴.Preferably, R⁴ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, halo, hydroxyl and—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. More preferably, R⁴ is hydrogen, C₁₋₄alkyl or —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. Preferably, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶ and R¹⁷ is independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ areindependently hydrogen or alkyl, and R¹¹ is selected from the groupconsisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl, benzyland substituted benzyl. More preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ are independently hydrogen or C₁₋₄alkyl, and R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), A is N.

In still embodiment of a compound of Formula (I), B is CR⁵. Preferably,R⁵ is selected from the group consisting of hydrogen, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, halo, hydroxyl and—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. More preferably, R⁵ is hydrogen, C₁₋₄alkyl or —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. Preferably, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶ and R¹⁷ is independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ areindependently hydrogen or alkyl, and R¹¹ is selected from the groupconsisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl, benzyland substituted benzyl. More preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ are independently hydrogen or C₁₋₄ alkyl, and R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), B is N.

In still other embodiments of a compound of Formula (I), D is CR⁶.Preferably, R⁶ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, halo, hydroxyl and—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. More preferably, R⁶ is hydrogen, C₁₋₄alkyl or —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. Preferably, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶ and R¹⁷ is independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ areindependently hydrogen or alkyl, and R¹¹ is selected from the groupconsisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl, benzyland substituted benzyl. More preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ are independently hydrogen or C₁₋₄ alkyl, and R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), D is N.

In still other embodiments of a compound of Formula (I), E is CR⁷.Preferably, R⁷ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, halo, hydroxyl and—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. More preferably, R⁷ is hydrogen, C₁₋₄alkyl or —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. Preferably, R⁷ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶ and R¹⁷ is independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ areindependently hydrogen or alkyl, and R¹¹ is selected from the groupconsisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl, benzyland substituted benzyl. More preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ are independently hydrogen or C₁₋₄ alkyl, and R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), E is N.

In still other embodiments of a compound of Formula (I), G is CR⁸.Preferably, R⁸ is selected from the group consisting of hydrogen, C₁₋₄alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, halo, hydroxyl and—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. More preferably, R⁸ is hydrogen, C₁₋₄alkyl or —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹. Preferably, R⁸ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴,R¹⁵, R¹⁶ and R¹⁷ is independently selected from the group consisting ofhydrogen, alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl andheteroaryl. Preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ areindependently hydrogen or alkyl, and R¹¹ is selected from the groupconsisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl, benzyland substituted benzyl. More preferably, R⁹, R¹⁰, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ are independently hydrogen or C₁₋₄ alkyl, and R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), G is N.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁵,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl, and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷is independently hydrogen or alkyl. Preferably, each of R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁶, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl, and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷is independently hydrogen or alkyl. Preferably, each of R⁵, R⁶ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl, and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷is independently hydrogen or alkyl. Preferably, each of R⁵, R⁶ and R⁷ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶ and R⁷ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is N, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl, and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷is independently hydrogen or alkyl. Preferably, each of R⁶ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁶ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, each of R⁵, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen orC₁₋₁₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl, and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷is independently hydrogen or alkyl. Preferably, each of R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁶, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴, R⁶ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴, R⁶ and R⁷ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶ and R⁷ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁶ and R⁷ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁶ and R⁷ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is N, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴ k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁷ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N. B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁵ and R⁷ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵ and R⁷ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (1), n is 0, Y is abond. A is N, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁵ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is CR⁴, B is N, D is CR⁶, E is N, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁴ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴ and R⁸ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is abond, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, each of R⁵ and R⁷ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵ and R⁷ arehydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ andR¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁵,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, each of R⁵, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴ k is 1, Z is NR¹⁷, r is 1 and eachof R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹,R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 0, Y is O,A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹,R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,C is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 1 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 2 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁵, R⁶, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably, R¹⁸ is hydrogen ormethyl. Preferably, each of R⁶, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁶, R⁷ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably, R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁵, R⁷ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably, R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵, R⁶ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁵, R⁶ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably, R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵, R⁶ and R⁷ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁵, R⁶ and R⁷ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is N, R⁴ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴ and R⁶ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably, R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably, R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴ and R⁶ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴ and R⁶ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is I, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, each of R⁵, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is -0W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris 2, and each of R⁹, R¹⁰, R¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is I, Z is O, r is2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 1 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 2 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁶, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁶, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁶, R⁷ and R⁸ is hydrogen. Preferably, eachof R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁴, R⁷ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴, R⁶ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁴, R⁶ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴, R⁵ and R⁷ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁴, R⁵ and R⁷ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁶ and R⁷ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁶ and R⁷ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is N, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N. B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁵ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁶ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁶ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁶ and R⁸ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (1), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is N, E is CR⁷, G is N, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴ and R⁸ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably R¹⁸ isselected from the group consisting of hydrogen, C₁₋₄ alkyl, phenyl,substituted phenyl, benzyl and substituted benzyl. More preferably, R¹⁸is hydrogen or methyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,C is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is I, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z isNR¹⁷, r is 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogenor C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independentlyhydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹¹)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O,r is 2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris I, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, ris 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is1, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is2, and each of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,C is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is O, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 1 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isNR¹⁷, r is 2 and each of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 1, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, ris 2, and each of R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, each of R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 1, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷,G is CR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁵, R⁷ andR⁸ is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄alkoxycarbonyl, carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z isCR¹⁵R¹⁶, r is 2, and each of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ isindependently hydrogen or C₁₋₄ alkyl. Preferably, each of R⁴, R⁵, R⁷ andR⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷and R⁸ are hydrogen. Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁵, R⁷ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is N, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁷ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴, R⁷ and R⁸ is independently hydrogen orC₁₋₄ alkyl. More preferably, R⁴, R⁷ and R⁸ are hydrogen. Preferably,each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independentlyhydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is CR⁶, E is CR⁷, G is N, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵ and R⁷ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵ and R⁷ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵ and R⁷ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is N, B is CR⁵, D is CR⁶, E is N, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁵ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵ and R⁸ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is abond, R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is N. D is CR⁶, E is N, G is CR⁸, R⁶ is—W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴ and R⁸ is independentlyhydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl, carboxyl, haloor hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ isindependently hydrogen or alkyl. Preferably R¹⁸ is selected from thegroup consisting of hydrogen, C₁₋₄ alkyl, phenyl, substituted phenyl,benzyl and substituted benzyl. More preferably R¹⁸ is hydrogen ormethyl. Preferably, each of R⁴ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴ and R⁸ are hydrogen. Preferably, each of R⁹,R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen orC₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁴ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁵,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹ each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁴ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁵, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁵ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably, each of R⁴,R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. More preferably,R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹²,R¹³, R¹⁴, R¹⁵, R¹⁶ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, each of R⁵, R⁶, R⁷ and R⁸ is hydrogen.Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁵, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, each of R⁴, R⁶, R⁷ and R⁸ is hydrogen. Preferably, R¹¹ ishydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is I, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁵ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁶, R⁷, and R⁸is independently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁶, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁶, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, andheteroaryl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G is CR⁸, R⁶ isW[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl and each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵,R¹⁶ and R¹⁷ is independently hydrogen or alkyl. Preferably R¹⁸ isselected from the group consisting of hydrogen, C₁₋₄ alkyl, phenyl,substituted phenyl, benzyl and substituted benzyl. More preferably, R¹⁸is hydrogen or methyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen or C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸are hydrogen. Preferably, each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁴, R¹⁵, R¹⁶and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 1, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is NR¹⁷, r is 2, andeach of R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 1, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is a bond, k is 1, Z is O, r is 2, andeach of R⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is NR¹⁷, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁷ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 1, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is O, r is 2, and each ofR⁹, R¹⁰ and R¹¹ is independently hydrogen or C₁₋₄ alkyl. Preferably,each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄ alkyl. Morepreferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, R¹¹ is hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is O, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 1 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is NR¹⁷, r is 2 andeach of R⁹, R¹⁰, R¹¹, R¹⁴ and R¹⁷ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴ and R¹⁷ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is O, r is 1, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR⁴, k is 1, Z is O, r is 2, and eachof R⁹, R¹⁰, R¹¹ and R¹⁴ is independently hydrogen or C₁₋₄ alkyl.Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogen or C₁₋₄alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen. Preferably, eachof R¹¹ and R¹⁴ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁴, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 1, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵ and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

In still other embodiments of a compound of Formula (I), n is 1, Y is O,R¹⁸ is hydrogen or methyl, A is CR⁴, B is CR⁵, D is CR⁶, E is CR⁷, G isCR⁸, R⁶ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹, each of R⁵, R⁵, R⁷ and R⁸ isindependently hydrogen, C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkoxycarbonyl,carboxyl, halo or hydroxyl, W is NR¹⁴, k is 1, Z is CR¹⁵R¹⁶, r is 2, andeach of R⁹, R¹⁰, R¹¹, R¹⁴, R¹⁵and R¹⁶ is independently hydrogen or C₁₋₄alkyl. Preferably, each of R⁴, R⁵, R⁷ and R⁸ is independently hydrogenor C₁₋₄ alkyl. More preferably, R⁴, R⁵, R⁷ and R⁸ are hydrogen.Preferably, R¹¹, R¹⁴, R¹⁵ and R¹⁶ are hydrogen.

Compounds of structural Formula (I) may be substrates for intestinalanion transporters such as the sodium-dependent multivitamin transporter(“SMVT”) and members of the proton-dependent monocarboxylate transporter(“MCT”) family. The SMVT transporter typically mediates the intestinalabsorption of the water-soluble vitamins pantothenate and biotin whereasnatural substrates for intestinally expressed monocarboxylatetransporters include lactate and pyruvate (Wang et al., J. Biol. Chem.1999, 274, 14875-14883; Halestrap et al., Biochem. J. 1999, 343,281-299). The intestinal permeability of certain monocarboxylate drugs(e.g., carindacillin, atorvastatin, etc.) may be mediated viainteraction with MCTs. Monocarboxylate transporter 1 (“MCT1”) expressionextends from the upper regions of the mammalian gastrointestinal tractthrough the large intestine, where it plays a role in absorption ofshort-chain fatty acids (e.g., butyrate) produced by colonic bacteria.Molecules transported by such colonically expressed proteins arecandidates for formulation in sustained oral delivery systems, wherecontrolled release of the drug during its prolonged residence in thecolon leads to sustained systemic drug levels relative to conventionalimmediate release formulations. Similarly, compounds that passivelydiffuse across the colonic mucosa may be administered via oral sustainedrelease formulations.

Methods for determining whether compounds may serve as substrates forthe SMVT transporter are disclosed in Example 3 herein (see Section 5).

4.3 Synthesis

Compounds disclosed herein may be obtained via the synthetic methodsillustrated in Schemes 1-7. Compounds of Formula (I) where n is 0, Y isa bond or CR¹R², W is a bond, k is 1, Z is O or NR¹⁷ and R¹¹ ishydrogen, i.e., compound (7), are prepared according to methodsillustrated in Scheme 1. The aromatic or heteroaromatic carboxylic acidcompound (2) is first converted into a reactive acylating agent (3), bytreatment with a phosgene equivalent, thionyl halide or relatedactivating agent. Reaction with propofol in the presence of base, andoptionally a catalyst such as DMAP, affords bis-ester (4). Removal ofthe carboxylate protecting group, conversion to a reactive acylatingagent by treatment with an appropriate coupling reagent, followed byaddition of protected amino acid or hydroxyl acid (5) generates compound(6). Finally, removal of the carboxylate protecting group affords thedesired compound (7).

Alternatively, ortho-disubstituted aromatic or heteroaromaticderivatives related to compound (7), i.e., compound (10), can beexpediently prepared starting with anhydride compound (8), asillustrated in Scheme 2.

Compounds of Formula (I) where n is 0, Y is a bond or CR¹R², W is O orNR¹⁴, k is 1, Z is CR¹⁵R¹⁶, O or NR¹⁷ and R¹¹ is hydrogen, i.e.,compound (16), are prepared according to methods illustrated in Scheme3. The aromatic or heteroaromatic carboxylic acid compound (11) is firstconverted into a reactive acylating agent (12), by treatment with aphosgene equivalent, thionyl halide or related activating agent.Reaction with propofol in the presence of base, and optionally acatalyst such as DMAP, affords ester (13). Removal of the protectinggroup from either the oxygen or nitrogen atom in (13), followed bytreatment with acylating agent (14) or (15) affords, after deprotectionof the carboxylate moiety, compound (16).

Compounds of Formula (I) where n is 0, Y is O or NR³, W is a bond, k is1, Z is O or NR¹⁷ and R¹¹ is hydrogen, i.e., compound (20), are preparedaccording to methods illustrated in Scheme 4. The phenolic or anilinocompound (17) is reacted with a phosgene equivalent to give respectivelythe chloroformate or amidoyl chloride species (18). Displacement of thechloro group by treatment with propofol in the presence of base, andoptionally a catalyst like DMAP, affords carbonate or carbamate (19).Alternatively, compound (19) can be elaborated directly from compound(17) by reaction with the propofol chloroformate derivative (31).Coupling of the carboxyalkyl moiety (5) proceeds as previously describedto afford compound (20).

Compounds of Formula (I) where n is 0, Y is O or NR³, W is O or NR¹⁴, kis 1, Z is CR¹⁵R¹⁶, O or NR¹⁷ and R¹¹ is hydrogen, i.e., compound (24),are prepared in an analogous fashion from compound (21), as illustratedin Scheme 5.

Compounds of Formula (I) where n is 1, Y is a bond or CR¹R², W is abond, k is 1, Z is O or NR¹⁷ and R¹¹ is hydrogen, i.e., compound (27),are prepared according to methods illustrated in Scheme 6. Theacyloxyalkyl ether (26) is prepared from aromatic or heteroaromaticcarboxylic acid compound (2), either by sequential halide displacementsof compound (32) in the presence of a base or metal promoter agent(typically a soluble Ag⁺ or Hg²⁺ salt), or by reaction with thehaloalkyl (or thioalkyl) propofol ether (33). If X₂ in (25) is —SR(e.g., thiomethyl), activation by treatment with sulfuryl chloride orsimilar halogenating agents precedes displacement by propofol togenerate compound (26). Coupling of the carboxyalkyl moiety (5) proceedsas previously described to afford compound (27).

Compounds of Formula (I) where n is 1, Y is a bond or CR¹R², W is O orNR¹⁴, k is 1, Z is CR¹⁵R¹⁶, O or NR¹⁷ and R¹¹ is hydrogen, i.e.,compound (30), are prepared according to methods illustrated in Scheme7. The acyloxyalkyl ether (29) is prepared from (11), either bysequential halide displacements of compound (32) under conditionspreviously described (i.e., in the presence of base or with a metal saltpromoter), or by reaction with the haloalkyl (or thioalkyl) propofolether (33). Removal of the protecting group from either the oxygen ornitrogen atom in (29), followed by treatment with acylating agent (14)or (15) affords, after deprotection of the carboxylate moiety, compound(30).

5.4 Therapeutic/Prophylactic Uses of the Compounds and Modes ofAdministration

The compounds described herein, may be used to treat and/or preventmigraine in patients. The methods comprise administering to a patient atherapeutically effective amount of a compound to treat or preventmigraine. In the therapeutic methods disclosed herein, a therapeuticallyeffective amount of the compound is administered to a patient sufferingfrom a migraine headache. In the prophylactic methods disclosed herein atherapeutically effective amount of the compound is administered to apatient at risk of developing a migraine.

In some embodiments, compounds disclosed herein are administered orallyto treat or prevent migraine. However, in other embodiments, compoundsdisclosed herein are administered parenterally (e.g., via inhalation orinjection). In some embodiments, compounds are administered in amountsof between about 10 mg to about 2 g to treat or prevent migraine.

Compounds disclosed herein may also be used as anti-emetics and can beadministered to patients at risk of vomiting or who are nauseous. Forexample, compounds disclosed herein may be administered to patients thatare being concurrently treated with various chemotherapy agents and/orsurgical procedures, which induce nausea. Accordingly, methods fortreating and preventing nausea and vomiting are provided. Typically, atherapeutically effective amount of a compound disclosed herein isadministered to a patient to treat or prevent nausea and vomiting.

In some embodiments, compounds are administered orally to treat orprevent nausea or vomiting. However, in other embodiments, compounds areadministered parenterally (e.g., via inhalation or injection to treat orprevent nausea or vomiting. In some embodiments, compounds areadministered in amounts of between about 10 mg to about 2 g to treat orprevent nausea or vomiting.

Compounds may also be used as hypnotic agents to induce and/or maintaingeneral anesthesia and/or as a sedative. Typically, a therapeuticallyeffective amount of compound is administered to a patient to inducehypnosis.

In some embodiments, compounds are administered intravenously when usedas a general anesthetic. In other embodiments, compounds areadministered by inhalation. Compounds may be formulated by the samemethods used to formulate propofol, which are well known in the art. Insome embodiments, compounds are formulated as an aqueous solution, whichcontains significantly less emulsifiers or solubilizers than used inaqueous formulations of propofol.

In some embodiments, compounds are administered orally in amounts ofabout 10 mg to 2 g daily when used as a sedative (e.g., for thetreatment of anxiety conditions). However, in other embodiments,compound may also be administered by inhalation, intravenously orintramuscularly when used as a sedative.

Compounds disclosed herein may be administered in similar amounts and inthe same schedule as described in the art for propofol. In someembodiments, dosage levels of compounds for producing generalanesthesia, maintaining anesthesia and producing a sedative effect areas described in the art for propofol.

Compounds may also be used to inhibit oxidation in biological materials.The methods involve contacting the biological material with an effectiveamount of the compound. In therapeutic methods disclosed herein, atherapeutically effective amount of the compound is administered to apatient suffering from a pathological condition treated by inhibition ofoxidation. In prophylactic methods disclosed herein a therapeuticallyeffective amount of the compound is administered to a patient at risk ofdeveloping a disease as a result of exposure to oxidative stress.Compounds disclosed herein may find particular use in preventing ortreating oxidation in disorders of the central nervous system thatinvolve an inflammatory component.

Compounds disclosed herein may be used to treat or preventneurodegenerative conditions of the nervous system, which include, butare not limited to, Friedrich's disease, Parkinson's disease,Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis(ALS), multiple sclerosis (MS) and Pick disease. In some embodiments, atherapeutically effective amount of a compound (e.g., between about 10mg to about 2 g daily) is orally administered to treat or preventchronic neurodegenerative diseases.

Compounds disclosed herein may also be used to treat trauma to thecentral nervous system such as, for example, skull fracture and itsresulting edema, concussion, contusion, brain hemorrhages, shearinglesions, subdural and epidural hematoma, and spinal cord injury (e.g.,mechanical injury due to compression or flexion of the spinal cord). Insome embodiments, a compound is parenterally administered by intravenousinjection or injection directly into the central nervous system (i.e.,intrathecally (“IT”) or into the brain) to treat or prevent traumaticconditions of the central nervous system. In other embodiments, atherapeutically effective amount of a compound (e.g., between about 25mg to about 500 mg IV or IM and between about 5 mg to about 100 mg IT)are administered to treat or prevent traumatic conditions of the centralnervous system.

Compounds may also be used as anti-convulsives to treat or preventseizures (e.g., epileptic seizures). Methods for treating or preventingconvulsions, which comprise administering a therapeutically effectiveamount of a compound disclosed herein to a patient in need of suchtreatment are provided. In some embodiments, compounds are administeredorally to treat or prevent convulsions. In other embodiments, compoundsare parenterally administered to treat or prevent convulsions. In otherembodiments, compounds are administered in amounts of between about 10mg to about 2 g daily to treat or prevent convulsions.

When used to treat or prevent the above disease or disorders compoundsand/or pharmaceutical compositions thereof may be administered orapplied singly, in combination with other agents. Compounds and/orpharmaceutical compositions thereof may also be administered or appliedsingly, in combination with other pharmaceutically active agents,including other compounds disclosed herein.

Methods of treatment and prophylaxis by administration to a patient of atherapeutically effective amount of a compound or pharmaceuticalcomposition thereof are provided herein. The patient may be an animal,is more preferably a mammal, and most preferably, a human.

The present compounds and/or pharmaceutical compositions thereof, arepreferably administered orally. Compounds and/or pharmaceuticalcompositions thereof may also be administered by any other convenientroute, for example, by infusion or bolus injection, by absorptionthrough epithelial or mucocutaneous linings (e.g., oral mucosa, rectaland intestinal mucosa, etc.). Administration can be systemic or local.Various delivery systems are known, (e.g., encapsulation in liposomes,microparticles, microcapsules, capsules, etc.) that can be used toadminister compounds and/or pharmaceutical composition thereof. Methodsof administration include, but are not limited to, intradermal,intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal,epidural, oral, sublingual, intranasal, intracerebral, intravaginal,transdermal, rectally, by inhalation, or topically, particularly to theears, nose, eyes, or skin.

In specific embodiments, it may be desirable to administer one or morecompounds and/or pharmaceutical composition thereof locally to the areain need of treatment. This may be achieved, for example, and not by wayof limitation, by local infusion during surgery, topical application,e.g., in conjunction with a wound dressing after surgery, by injection,by means of a catheter, by means of a suppository, or by means of animplant, said implant being of a porous, non-porous, or gelatinousmaterial, including membranes, such as sialastic membranes, or fibers.

In certain embodiments, it may be desirable to introduce one or morecompounds and/or pharmaceutical compositions thereof into the centralnervous system by any suitable route, including intraventricular,intrathecal and epidural injection. Intraventricular injection may befacilitated by an intraventricular catheter, for example, attached to areservoir, such as an Ommaya reservoir.

In some embodiments, compounds and/or pharmaceutical compositionsthereof can be delivered via sustained release systems, preferably, oralsustained release systems. In some embodiments, a pump may be used (seeLanger, supra; Sefton, 1987, CRC Crit Ref Biomed Eng. 14:201; Saudek etal., 1989, N. Engl. J. Med. 321:574).

In other embodiments, polymeric materials can be used (see “MedicalApplications of Controlled Release,” Langer and Wise (eds.), CRC Pres.,Boca Raton, Fla. (1974); “Controlled Drug Bioavailability,” Drug ProductDesign and Performance, Smolen and Ball (eds.), Wiley, New York (1984);Langer et al., 1983, J Macromol. Sci. Rev. Macromol Chem. 23:61; seealso Levy et al., 1985, Science 228: 190; During et al., 1989, Ann.Neurol. 25:351; Howard et al., 1989, J. Neurosurg. 71:105). In stillother embodiments, polymeric materials are used for oral sustainedrelease delivery. Such polymers include, for example, sodiumcarboxymethylcellulose, hydroxypropylcellulose,hydroxypropylmethylcellulose and hydroxyethylcellulose. Other celluloseethers have been described (Alderman, Int. J. Pharm. Tech. & Prod. Mfr.1984, 5(3) 1-9). Factors affecting drug release are well known to theskilled artisan and have been described in the art (Bamba et al., Int.J. Pharm. 1979, 2, 307).

In other embodiments, enteric-coated preparations are used for oralsustained release administration. Coating materials include, forexample, polymers with pH-dependent solubility (i.e., pH-controlledrelease), polymers with slow or pH-dependent rate of swelling,dissolution or erosion (i.e., time-controlled release), polymers thatare degraded by enzymes (i.e., enzyme-controlled release) and polymersthat form firm layers that are destroyed by an increase in pressure(i.e., pressure-controlled release).

In still other embodiments, osmotic delivery systems are used for oralsustained release administration (Verma et al., Drug Dev. Ind. Pharm.2000, 26:695-708). In some embodiments, OROS™ osmotic devices are usedfor oral sustained release delivery devices (Theeuwes et al., U.S. Pat.No. 3,845,770; Theeuwes et al., U.S. Pat. No. 3,916,899).

For administration by inhalation, compounds may be convenientlydelivered to the lung by a number of different devices. For example, aMetered Dose Inhaler (“MDI”) which utilizes canisters that contain asuitable low boiling propellant, e.g., dichlorodifluoromethane,trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide orother suitable gas may be used to deliver compounds disclosed hereindirectly to the lung.

Alternatively, a Dry Powder Inhaler (“DPI)” device may be used toadminister compounds to the lung (See, e.g., Raleigh et al., Proc. Amer.Assoc. Cancer Research Annual Meeting, 1999, 40, 397). DPI devicestypically use a mechanism such as a burst of gas to create a cloud ofdry powder inside a container, which may then be inhaled by the patient.A popular variation is the multiple dose DPI (“MDDPI”) system, whichallows for the delivery of more than one therapeutic dose. For example,capsules and cartridges of gelatin for use in an inhaler or insufflatormay be formulated containing a powder mix of a compound and a suitablepowder base such as lactose or starch for these systems.

Another type of device that may be used to deliver compounds to the lungis a liquid spray device supplied, for example, by Aradigm Corporation,Hayward, Calif. Liquid spray systems use extremely small nozzle holes toaerosolize liquid drug formulations that may then be directly inhaledinto the lung.

In some embodiments, a nebulizer device is used to deliver a compounddisclosed herein to the lung. Nebulizers create aerosols from liquiddrug formulations by using, for example, ultrasonic energy to form fineparticles that may be readily inhaled (see e.g., Verschoyle et al.,British J. Cancer, 1999, 80, Suppl. 2, 96). Examples of nebulizersinclude devices supplied by Batelle Pulmonary Therapeutics (Columbus,Ohio) (See, Armer et al., U.S. Pat. No. 5,954,047; van der Linden etal., U.S. Pat. No. 5,950,619; van der Linden et al., U.S. Pat. No.5,970,974).

In still other embodiments, an electrohydrodynamic (“EHD”) aerosoldevice is used to deliver a compound to the lung. EHD aerosol devicesuse electrical energy to aerosolize liquid drug solutions or suspensions(see e.g., Noakes et al., U.S. Pat. No. 4,765,539; Coffee, U.S. Pat. No.4,962,885; Coffee, International Publication No. WO 94/12285; Coffee,International Publication No., WO 94/14543; Coffee, InternationalPublication No., WO 95/26234, Coffee, International Publication No., WO95/26235, Coffee, International Publication No., WO 95/32807).Electrochemical properties of a compound may be important parameters tooptimize when delivering this compound to the lung with an EHD aerosoldevice; such optimization is routinely performed by one of skill in theart. EHD aerosol devices may more efficiently deliver compounds to thelung than existing pulmonary delivery technologies. Other methods ofintra-pulmonary delivery of compounds are known to the skilled artisanand are within the scope of the present disclosure.

The compounds and/or pharmaceutical compositions thereof preferably,provide therapeutic or prophylactic levels of propofol upon in vivoadministration to a patient. While not wishing to bound by theory, thepromoiety or promoieties of the compounds may be cleaved eitherchemically and/or enzymatically. One or more enzymes present in thestomach, intestinal lumen, intestinal tissue, blood, liver, brain or anyother suitable tissue of a mammal may enzymatically cleave the promoietyor promoieties of the compounds disclosed herein. The mechanism ofcleavage is not important.

While not wishing to bound by theory, the promoiety or promoieties ofthe compounds disclosed herein may be cleaved prior to absorption by thegastrointestinal tract (e.g., within the stomach or intestinal lumen)and/or after absorption by the gastrointestinal tract (e.g., inintestinal tissue, blood, liver or other suitable tissue of a mammal).Propofol may remain conjugated to a promoiety during transit across theintestinal mucosal barrier to provide protection from presystemicmetabolism. In some embodiments, compounds are essentially notmetabolized to propofol within enterocytes, but are metabolized to theparent drug within the systemic circulation. Cleavage of the promoietyor promoieties of the compounds after absorption by the gastrointestinaltract, may allow these prodrugs to be absorbed into the systemiccirculation either by active transport, passive diffusion or by amixture of both active and passive processes. In some embodiments,compounds are actively absorbed through interaction with aniontransporters like SMVT or MCT's.

Cleavage of the promoiety or promoieties of compounds after absorptionby the gastrointestinal tract, may allow these prodrugs to be absorbedinto the systemic circulation from the large intestine. In someembodiments, the compounds and/or pharmaceutical compositions thereofare administered as sustained release systems. In other embodiments, thecompounds and/or pharmaceutical compositions thereof are delivered byoral sustained release administration. Preferably, in this embodiment,the compounds and/or pharmaceutical compositions are administered twiceper day (more preferably, once per day).

5.5 Pharmaceutical Compositions

The present pharmaceutical compositions contain a therapeuticallyeffective amount of one or more compounds, preferably in purified form,together with a suitable amount of a pharmaceutically acceptablevehicle, to provide the form for proper administration to a patient.When administered to a patient, the compounds and pharmaceuticallyacceptable vehicles are preferably sterile. Water is a preferred vehiclewhen a compound is administered intravenously. Saline solutions andaqueous dextrose and glycerol solutions can also be employed as liquidvehicles, particularly for injectable solutions. Suitable pharmaceuticalvehicles also include excipients such as starch, glucose, lactose,sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate,glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol,propylene, glycol, water, ethanol and the like. The presentpharmaceutical compositions, if desired, can also contain minor amountsof wetting or emulsifying agents, or pH buffering agents. In addition,auxiliary, stabilizing, thickening, lubricating and coloring agents maybe used.

Pharmaceutical compositions comprising a compound disclosed herein maybe manufactured by means of conventional mixing, dissolving,granulating, dragee-making, levigating, emulsifying, encapsulating,entrapping or lyophilizing processes. Pharmaceutical compositions may beformulated in conventional manner using one or more physiologicallyacceptable carriers, diluents, excipients or auxiliaries, whichfacilitate processing of compounds into preparations which can be usedpharmaceutically. Proper formulation is dependent upon the route ofadministration chosen.

The present compositions can take the form of solutions, suspensions,emulsion, tablets, pills, pellets, capsules, capsules containingliquids, powders, sustained-release formulations, suppositories,emulsions, aerosols, sprays, suspensions, or any other form suitable foruse. In some embodiments, the pharmaceutically acceptable vehicle is acapsule (see e.g., Grosswald et al., U.S. Pat. No. 5,698,155). Otherexamples of suitable pharmaceutical vehicles have been described in theart (see Remington's Pharmaceutical Sciences, Philadelphia College ofPharmacy and Science, 19th Edition, 1995). In other embodiment,pharmaceutical compositions are formulated for oral delivery.

Pharmaceutical compositions for oral delivery may be in the form oftablets, lozenges, aqueous or oily suspensions, granules, powders,emulsions, capsules, syrups, or elixirs, for example. Orallyadministered pharmaceutical compositions may contain one or moreoptional agents, for example, sweetening agents such as fructose,aspartame or saccharin, flavoring agents such as peppermint, oil ofwintergreen, or cherry coloring agents and preserving agents, to providea pharmaceutically palatable preparation. Moreover, where in tablet orpill form, the pharmaceutical compositions may be coated to delaydisintegration and absorption in the gastrointestinal tract, therebyproviding a sustained action over an extended period of time.Selectively permeable membranes surrounding an osmotically activedriving compound are also suitable for orally administered compounds andpharmaceutical compositions. In these later platforms, fluid from theenvironment surrounding the capsule is imbibed by the driving compound,which swells to displace the agent or agent composition through anaperture. These delivery platforms can provide an essentially zero orderdelivery profile as opposed to the spiked profiles of immediate releaseformulations. A time delay material such as glycerol monostearate orglycerol stearate may also be used. Oral compositions can includestandard vehicles such as mannitol, lactose, starch, magnesium stearate,sodium saccharine, cellulose, magnesium carbonate, etc. Such vehiclesare preferably of pharmaceutical grade.

For oral liquid preparations such as, for example, suspensions, elixirsand solutions, suitable carriers, excipients or diluents include water,saline, alkyleneglycols (e.g., propylene glycol), polyalkylene glycols(e.g., polyethylene glycol) oils, alcohols, slightly acidic buffersbetween pH 4 and pH 6 (e.g., acetate, citrate, ascorbate at betweenabout 5 mM to about 50 mM), etc. Additionally, flavoring agents,preservatives, coloring agents, bile salts, acylcarnitines and the likemay be added.

Compounds may also be formulated in rectal or vaginal pharmaceuticalcompositions such as suppositories or retention enemas, e.g., containingconventional suppository bases such as cocoa butter or other glycerides.

In addition to the formulations described previously, compounds may alsobe formulated as a depot preparation. Such long acting formulations maybe administered by implantation (for example, subcutaneously orintramuscularly) or by intramuscular injection. Thus, for example,compounds may be formulated with suitable polymeric or hydrophobicmaterials (for example, as an emulsion in an acceptable oil) or ionexchange resins, or as sparingly soluble derivatives, for example, as asparingly soluble salt.

When a compound is acidic, it may be included in any of theabove-described formulations as the free acid, a pharmaceuticallyacceptable salt, a solvate or hydrate. Pharmaceutically acceptable saltssubstantially retain the activity of the free acid, may be prepared byreaction with bases and tend to be more soluble in aqueous and otherprotic solvents than the corresponding free acid form.

Liquid drug formulations suitable for use with nebulizers and liquidspray devices and EHD aerosol devices will typically include a compoundwith a pharmaceutically acceptable carrier. The pharmaceuticallyacceptable carrier may be a liquid such as alcohol, water, polyethyleneglycol or perfluorocarbon. Optionally, another material may be added toalter the aerosol properties of the solution or suspension of compoundsdisclosed herein. Preferably, this material is liquid such as analcohol, glycol, polyglycol or fatty acid. Other methods of formulatingliquid drug solutions or suspension suitable for use in aerosol devicesare known to those of skill in the art (see, e.g., Biesalski, U.S. Pat.No. 5,112,598; Biesalski, U.S. Pat. No. 5,556,611).

5.6 Combination Therapy

In certain embodiments, the compounds disclosed herein can be used incombination therapy with at least one other therapeutic agent. Thecompound and the therapeutic agent can act additively or, morepreferably, synergistically. In some embodiments, a pharmaceuticalcomposition comprising a compound disclosed herein is administeredconcurrently with the administration of another therapeutic agent, whichcan be part of the same pharmaceutical composition a or a differentpharmaceutical composition. In other embodiments, a pharmaceuticalcomposition comprising a compound disclosed herein is administered prioror subsequent to administration of another therapeutic agent.

6. EXAMPLES

The following examples, further define the disclosure and describe indetail preparation of compounds, pharmaceutical compositions thereof andassays for using compounds and pharmaceutical compositions. It will beapparent to those skilled in the art that many modifications, both tomaterials and methods, may be practiced without departing from the scopeof the invention.

In the examples below, the following abbreviations have the followingmeanings. If an abbreviation is not defined, it has its generallyaccepted meaning.

-   -   Atm=atmosphere    -   Boc=tert-butyloxycarbonyl    -   Bzl=benzyl    -   Cbz=carbobenzyloxy    -   DCC=dicyclohexylcarbodiimide    -   DMAP=4-N,N-dimethylaminopyridine    -   DMEM=Dulbecco's minimun eagle medium    -   DMF=N,N-dimethylformamide    -   DMSO=dimethylsulfoxide    -   Fmoc=9-fluorenylmethyloxycarbonyl    -   g=gram    -   h=hour    -   HBSS=Hank's buffered saline solution    -   L=liter    -   LC/MS=liquid chromatography/mass spectroscopy    -   M=molar    -   min=minute    -   mL=milliliter    -   mmol=millimoles    -   NHS=N-hydroxysuccinimide    -   PBS=phosphate buffered saline    -   THF=tetrahydrofuran    -   TFA=trifluoroacetic acid    -   TMS=trimethylsilyl    -   μL=microliter    -   μM=micromolar    -   v/v=volume to volume

Example 13-{[2-[2,6-Bis(isopropyl)phenoxycarbonyl]-benzoyl]amino}-propanoic Acid(101) STEP A: 2-[2,6-Bis(isopropyl)phenoxycarbonyl]-benzoic Acid (102)

To a mixture of phthalic anhydride (0.84 g, 5.6 mmol) and propofol (1 g,5.6 mmol) was added triethylamine (0.65 g, 6.4 mmol) and a catalyticamount of DMAP. The reaction mixture was brought to 90° C., stirred for14 h, cooled to room temperature and diluted with ethyl ether (100 mL).The organic layer was washed with 10% aqueous citric acid solution (2×50mL). The phases were separated and the organic phase was dried overMgSO₄ and concentrated in vacuo. The crude product was sufficiently pureto be carried to the subsequent step.

STEP B:3-{[2-[2,6-Bis(isopropyl)phenoxycarbonyl]-benzoyl]amino}-propanoic Acid(101)

To a solution containing (102) (2.1 g, 6.4 mmol) and beta-alaninetert-butyl ester hydrochloride (1.16 g, 6.4 mmol) in DMF (20 mL) wasadded diisopropylethylamine (2.4 mL, 13.7 mmol) followed byO-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(2.5 g, 6.5 mmol). The resulting reaction mixture was stirred at roomtemperature for 14 h, diluted with ethyl acetate (100 mL), washed with10% aqueous citric acid solution (50 mL), followed by saturated aqueousNaHCO₃ solution (50 mL) and brine (2×50 mL). The organic phase was driedover MgSO₄ and concentrated in vacuo. The crude residue was dissolved inanhydrous dichloromethane (30 mL) and cooled to 0° C. before a solutionof hydrochloric acid (10 mL, 4 N in dioxane) was added. The reaction wasstirred for 1 h at 0° C. and 1 h at room temperature. The solvent wasremoved in vacuo and the crude residue was purified by preparative LC/MSto afford 0.85 g (38% yield over three steps) of the title compound(101). ¹H NMR (400 MHz, CD₃OD): δ 8.20 (dd, J=7.6, 0.8 Hz, 1H),7.70-7.68 (m, 1H), 7.63-7.59 (m, 1H), 7.49 (dd, J=7.6, 0.8 Hz, 1H),7.22-7.17 (m, 3H), 3.54 (t, J=7.2 Hz, 2H), 3.06-3.00 (m, 2H), 2.57 (t,J=6.8 Hz, 2H), 1.19 (d, J=6.8 Hz, 12H). MS (ESI) m/z 398.3 (M+H⁺).

EXAMPLE 23-{[2-[2,6-Bis(isopropyl)phenoxycarbonyloxy]-benzoyl]amino}-propanoicAcid (103) STEP A: 2,6-Bis(isopropyl)phenoxycarbonyl Chloride (104)

Phosgene (13 mL, 20% in toluene) was added to propofol (3.6 g, 20 mmol)under a nitrogen atmosphere. The mixture was cooled to 0° C. andN,N-dimethylaniline (3.3 mL, 26 mmol) was added dropwise. The reactionmixture was allowed to warm to room temperature slowly and stirred for14 h. The solvent was removed in vacuo. The crude product was carried tonext step without further purification.

STEP B: Benzyl 2-[2,6-Bis(isopropyl)phenoxycarbonyloxy]-benzoate (105)

To a cooled (0° C.) solution of benzyl salicylate (0.77 g, 3.3 mmol) indichloromethane (6 mL) was added triethylamine (0.52 mL, 3.7 mmol) and acatalytic amount of DMAP. To this mixture a suspension of compound (104)(0.9 g, 3.7 mmol, crude product from last step) in dichloromethane (4mL) was further added. The reaction was allowed to warm to roomtemperature slowly and stirred for 14 h. The reaction mixture was thendiluted with 10% aqueous citric acid solution (10 mL) and extracted withethyl ether (2×40 mL). The organic phase was dried over MgSO₄ andconcentrated in vacuo. The residue was purified by radial chromatographyon silica gel (eluting with ethyl acetate/hexane) to afford 0.8 g (57%yield over two steps) of the title compound (105).

STEP C: 2-[2,6-Bis(isopropyl)phenoxycarbonyloxy]-benzoic Acid (106)

To a suspension of 10% Pd—C (100 mg) in ethyl acetate (15 mL) undernitrogen was added a solution of compound (105) (0.7 g, 1.6 mmol) inethyl acetate (5 mL). The resulting suspension was degassed three timesand then hydrogen gas was introduced. The reaction mixture was stirredunder 1 atm hydrogen atmosphere for 14 h, then filtered through a smallplug of celite. The filtrate was concentrated in vacuo. The crudeproduct (106) was carried to next step without further purification.

STEP D:3-{[2-[2,6-Bis(isopropyl)phenoxycarbonyloxy]-benzoyl]amino}-propanoicAcid (103)

To a solution of crude compound (106) (0.4 g, 1.1 mmol) from above andbeta-alanine tert-butyl ester hydrochloride (0.2 g, 1.1 mmol) in DMF (5mL) was added diisopropylethylamine (0.41 mL, 2.3 mmol) followed byO-(benotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate(0.44 g, 1.1 mmol). The resulting reaction mixture was stirred at roomtemperature for 14 h, diluted with ethyl acetate (50 mL), washed with10% aqueous citric acid solution (30 mL), followed by saturated aqueousNaHCO₃ solution (30 mL) and brine (2×20 mL). The organic phase was driedover MgSO₄ and concentrated in vacuo. The crude residue was thendissolved in anhydrous dichloromethane (5 mL) and cooled to 0° C. beforea solution of hydrochloric acid (1 mL, 4 N in dioxane) was added. Thereaction was stirred for 2 h at 0° C. and the solvent was removed invacuo. The crude residue was purified by preparative LC/MS to afford 50mg (8% yield over three steps) of the title compound (103). ¹H NMR (400MHz, CDCl₃): δ 7.85 (dd, J=7.6, 1.6 Hz, 1H), 7.51-7.48 (m, 1H),7.34-7.13 (m, 5H), 3.72 (q, J=6.0 Hz, 2H), 3.13-3.10 (m, 2H), 2.67 (t,J=6.4 Hz, 2H), 1.25 (d, J=6.8 Hz, 121). MS (ESI) m/z 414.3 (M+H⁺).

EXAMPLE 3 Analysis of Electrogenic Transport in SMVT-Expressing XenopusOocytes

Transporter Cloning: The complete open reading frame of human SMVT(SLC5A6) was amplified from human cDNA prepared from intestinal mRNA.Gene-specific oligonucleotide primers were designed against Genbanksequences (NM-021095). Amplified PCR products were cloned into amodified version of the mammalian expression vector pcDNA3 (termed pMO)that was engineered to contain the 5′ and 3′ untranslated regions fromthe Xenopus beta-globin gene. All clones were completely sequenced andtested for function by transient transfection in HEK293 cells.Radiolabeled ³H biotin was used to assess SMVT function (see methodbelow).

Xenopus Oocyte Expression and Electrophysiology: cRNA for oocyteexpression was prepared by linearization of plasmid cDNA and in vitrotranscription using T7 polymerase (Epicentre Ampliscribe kit). Xenopusoocytes were prepared and maintained as previously described (Collins etal., Proc. Natl. Acad. Sci. 1997, 13:5456-5460) and injected with 10-30ng RNA. Transport currents were measured 2-6 days later usingtwo-electrode voltage-clamp (Axon Instruments). All experiments wereperformed using a modified oocyte ringers solution (90 mM NaCl, 2 mMKCl, 1.8 mM CaCl₂, 1 mM MgCl₂, and 10 mM NaHEPES, pH 7.4; in Na⁺-freesolutions 90 mM choline chloride was substituted for NaCl). The membranepotential of oocytes was held at −60 mV and current traces acquiredusing PowerLab software (ADInstruments). Full 7-concentrationdose-responses were performed for each compound. Current responses atthe highest concentration were normalized to the maximal biotin elicitedcurrents (i.e., at 0.5 mM). Half-maximal concentrations were calculatedusing non-linear regression curve fitting software (Prism) with the Hillco-efficient fixed to 1. To ensure that currents were specific for theover-expressed transporter, all compounds were tested against uninjectedoocytes. Since SMVT requires Na⁺ for transport, transport specificitywas confirmed by application of the compounds in a Na⁺-free solution.

Compound (101) elicited SMVT-specific currents significantly abovebackground (at least 10% of I_(max) for biotin) when tested at 0.5 mM onoocytes expressing SMVT, confirming that this compound serves as asubstrate for the transporter.

Finally, it should be noted that there are alternative ways ofimplementing the present invention. Accordingly, the disclosedembodiments are to be considered as illustrative and not restrictive,and the invention is not to be limited to the details given herein, butmay be modified within the scope and equivalents of the appended claims.All publications and patents cited herein are incorporated by reference.

1. A compound of Formula (I):

or pharmaceutically acceptable salts, hydrates, solvates or n-oxidesthereof, wherein: n is 0 or 1; Y is selected from the group consistingof a bond, CR¹R², NR³, O and S; A is CR⁴ or N; B is CR⁵ or N; D is CR⁶or N; E is CR⁷ or N; G is CR⁸ or N; R¹⁸ is selected from the groupconsisting of hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, aryl,substituted aryl, arylalkyl, carbamoyl, substituted carbamoyl,cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, heteroaryl,substituted heteroaryl and heteroarylalkyl; R¹ and R² are independentlyselected from the group consisting of hydrogen, alkyl, substitutedalkyl, aryl, substituted aryl, arylalkyl, cycloalkyl, substitutedcycloalkyl, cycloheteroalkyl, heteroaryl, substituted heteroaryl andheteroarylalkyl; R³ is selected from the group consisting of hydrogen,alkyl, substituted alkyl, aryl, arylalkyl, cycloalkyl and heteroaryl; R⁴is selected from the group consisting of hydrogen, alkyl, substitutedalkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substitutedaryl, arylalkyl, carboxy, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl,heteroarylalkyl, hydroxy and —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; R⁵ isselected from the group consisting of hydrogen, alkyl, substitutedalkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substitutedaryl, arylalkyl, carboxy, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl,heteroarylalkyl, hydroxy and —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; R⁶ isselected from the group consisting of hydrogen, alkyl, substitutedalkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substitutedaryl, arylalkyl, carboxy, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl,heteroarylalkyl, hydroxy and —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; R⁷ isselected from the group consisting of hydrogen, alkyl, substitutedalkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substitutedaryl, arylalkyl, carboxy, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl,heteroarylalkyl, hydroxy and —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; R⁸ isselected from the group consisting of hydrogen, alkyl, substitutedalkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, aryl, substitutedaryl, arylalkyl, carboxy, cycloalkyl, substituted cycloalkyl,cycloheteroalkyl, halo, heteroaryl, substituted heteroaryl,heteroarylalkyl, hydroxy and —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; W isselected from the group consisting of a bond, CR¹²R¹³, NR⁴, O and S; Zis selected from the group consisting of CR¹⁵R¹⁶, NR¹⁷, O and S; k is 0or 1; r is 1, 2 or 3; each of R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁵ and R¹⁶ isindependently selected from the group consisting of hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, cycloalkyl,substituted cycloalkyl, cycloheteroalkyl, heteroaryl, substitutedheteroaryl and heteroarylalkyl; R¹⁴ and R¹⁷ are independently selectedfrom the group consisting of hydrogen, alkyl, substituted alkyl, aryl,arylalkyl, cycloalkyl and heteroaryl; with the provisos that: at leastone of A, B, D, E and G is not N; one and only one of R⁴, R⁵, R⁶, R⁷ orR⁸ is —W[C(O)]_(k)Z(CR⁹R¹⁰)_(r)CO₂R¹¹; and if k is 0 then W is a bond.